In Phase I of this award I will obtain a Ph.D. in physiology investigating adrenergic receptors in horse airways for my thesis research. In Phase II, I will use techniques I have learned in Phase I to investigate adrenergic receptors in airways in some airway disease models. Our laboratory is presently studying airway reactivity in a group of ponies which develop airway obstruction when exposed to barn dust (principal) and in a group of age and sex matched normal ponies (controls). Principals develop airway hyperreactivity during attacks of airway obstruction but the hypereactivity does not appear to be due to decreased baseline airway caliber. In Phase I I propose to investigate one of the possible mechanisms of airway hyperreactivity in principal ponies, i.e., changes in adrenergic receptor activity and/or distribution. Studies will be conducted in both intact animals and in membrane preparations from lungs and airways. In intact ponies I will perform dose response studies of horse airways to alpha1, alpha2 and beta2 adrenergic agonists and/or antagonists. I will also investigate how these agonists and antagonists modulate the dose response to aerosol histamine. In membrane preparations I will use radioligand binding studies to determine the density and activity of adrenergic receptors. I will use autoradiography to localize receptors in lung and airway tissue. In phase II, I will perform similar experiments on at least two models of airway disease. One will be a hypersensitivity to ovalbumim the other a toxic disease induced by 3-methylindole. I may also use a model in which ponies are made hypersensitive to Micropolyspora faeni. These experiments will be unique because they will allow comparison of spontaneous and induced diseases in the same species.